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Objectives: This study aims to compare <I>in vivo</I> activity of benzoxazinorifamycin KRM-1648 (KRM) with those of rifampicin (RFP) and rifabutin (RBT) against experimental murine tuberculosis.<BR>Study design: Mice were infected with <I>Mycobacterium tuberculosis</I> or <I>M. bovis</I> by the intratracheal (IT) or intravenous (IV) routes, and treated for 10 days with various doses of each drug starting from the 8th or 11th day after the TB-infection.<BR>Results: (A) A rapid test for <I>in vivo</I> evaluation of three rifamycins was conducted by examining the survival days of treated mice infected with 10<SUP>6</SUP> cfu of <I>M. bovis</I> Ravenel. Mice treated with KRM exhibited 2.1-3.7 times longer survival times, in comparison with those treated with RFP or RBT. (B) In the IT-model of <I>M. bovis</I> Ravenel infection, three rifamycin derivatives gave "distinctive dose-response curves" in the correlation of dose sizes with the mean survival times or "log<SUB>10</SUB> CFU/lungs reductions". (C) In <I>M. tuberculosis</I> Kurono infection models, the ranking of the anti-TB activity of the three rifamycins in each organ was as follows: IT-and IV-lungs: KRM>RFP=RBT, IV-spleen: KRM≈≈RBT>RFP, IV-liver: KRM≈RBT>RFP. (D) Based on the results of"log<SUB>10</SUB>CFU reductions"in different organs in <I>M. tuberculosis</I> Kurono infection models, "characteristic in vivo activity patterns of each rifamycin" were obtained. (E) The therapeutic efficacy of KRM in lungs was greater than in spleen and liver with any dose. In contrast, RBT exhibited more remarkable <I>in vivo</I> activity in the spleen and liver than in lungs.<BR>Conclusion: The prominent <I>in vivo</I> activity of KRM may allow small dose for effective therapy;1/3 dose or less in comparison with those of RFP or RBT, or intermittent therapy of tuberculosis.